Parathyroid Hormone Suppression Research Articles

7660 Navigating Hypercalcemia: MAC Treatment Hurdles and the Unforeseen Impact of Vitamin D Supplementation

Abstract Disclosure: S. Noguchi: None. S. Lai: None. A. Rajpal: None. Introduction: Hypercalcemia is a recognized complication in granulomatous disorders such as sarcoidosis and tuberculosis, resulting from increased 1 alpha-hydroxylase activity in macrophages leading to excessive conversion to 1,25(OH)2 vitamin D (calcitriol). Mycobacterium avium complex (MAC) is an infectious granulomatous disease often suspected in immunocompromised individuals, including those with human immunodeficiency virus (HIV). Additionally, vitamin D deficiency is prevalent in the general population, prompting supplementation. We hereby present a patient with advanced HIV and disseminated MAC who developed severe calcitriol-induced hypercalcemia in the setting of high dose vitamin D supplementation. Case description: A 48-year-old male with advanced HIV (CD4 count <20 cells/mm^3) presented for evaluation of abdominal pain and constipation, and was found to have severe hypercalcemia of 14.8 mg/dL. Five months prior, he had restarted anti-retroviral therapy (ART) after having been out of care for over a year and was diagnosed with disseminated MAC for which he was on azithromycin and ethambutol. Cultures drawn during this admission were negative for MAC. Hypercalcemia was possibly due to paradoxical immune reconstitution inflammatory syndrome (IRIS) and with appropriate management his calcium level rapidly normalized to 9.7 mg/dL and remained stable until the recent admission. He represented one year later with a calcium level of 13.8 mg/dL with suppressed parathyroid hormone levels, which was refractory to bisphosphonate therapy, therefore was empirically initiated on dexamethasone. By day 4, his calcium levels improved significantly and was discharged on a taper regimen. Cultures collected this admission later revealed ongoing MAC infection, which raised concern for treatment failure and calcitriol-induced hypercalcemia. Calcitriol levels were elevated at 105 pg/mL, which further supported this hypothesis. Additionally, prior to admission he had been prescribed ergocalciferol 50,000 units weekly for 8 weeks, after which he was transitioned to 2,000 units daily. This likely exacerbated the calcitriol-induced hypercalcemia by providing sudden availability of substrate, 25-OH vitamin D, for the activated macrophages. Conclusion: ART has reduced the incidence of opportunistic infections such as MAC, however mortality remains high. Vigilant monitoring for complications, particularly life-threatening calcitriol-induced hypercalcemia and timely use of corticosteroids, is crucial. This case also highlights the need for careful oversight in high-dose vitamin D supplementation for individuals with granulomatous disease and vitamin D dysregulation. Presentation: 6/2/2024

Presentation and outcome in carriers of pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter NPT 2a and 2c

Pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter 2a and 2c are rare causes of phosphate wasting. Since data on presentation and outcomes are scarce, we collected clinical, biochemical and genetic data via an online questionnaire and the support of European professional organizations. One hundred thirteen patients (86% children) from 90 families and 17 countries with pathogenic or likely pathogenic variants in SLC34A1 or SLC34A3 and a median follow-up of three years were analyzed. Biallelic SLC34A1 variant carriers showed polyuria, failure to thrive, vomiting, constipation, hypercalcemia and nephrocalcinosis in infancy, while biallelic SLC34A3 carriers presented in childhood or even adulthood with rickets/osteomalacia and/or osteopenia/osteoporosis, hypophosphatemia and, less frequently, nephrocalcinosis, while the prevalences of kidney stones were comparable. Adult biallelic SLC34A3 carriers had a six-fold increase chronic kidney disease (CKD) prevalence compared to the general population. All biallelic variant carriers shared a common biochemical pattern including elevated 1,25(OH)2D and alkaline phosphatase levels, suppressed parathyroid hormone (PTH), and hypercalciuria. Heterozygous carriers showed similar but less pronounced phenotypes. In biallelic SLC34A1 carriers, an attenuation of clinical features was observed after infancy, independent of treatment. Phosphate treatment was given in 55% of patients, median duration two years, and resulted in significant reduction, although not normalization, of alkaline phosphatase and of hypercalciuria but an increase in PTH levels, while 1,25(OH)2D levels remained elevated. Thus, our study indicates that biallelic SLC34A1 and SLC34A3 carriers show distinct, albeit overlapping phenotypes, with the latter having an increased risk of CKD in adulthood. Phosphate treatment may promote kidney phosphate loss and enhance 1,25(OH)2D synthesis via increased PTH production.

Large library docking identifies positive allosteric modulators of the calcium-sensing receptor.

Positive allosteric modulator (PAM) drugs enhance the activation of the calcium-sensing receptor (CaSR) and suppress parathyroid hormone (PTH) secretion. Unfortunately, these hyperparathyroidism-treating drugs can induce hypocalcemia and arrhythmias. Seeking improved modulators, we docked libraries of 2.7 million and 1.2 billion molecules against the CaSR structure. The billion-molecule docking found PAMs with a 2.7-fold higher hit rate than the million-molecule library, with hits up to 37-fold more potent. Structure-based optimization led to nanomolar leads. In ex vivo organ assays, one of these PAMs was 100-fold more potent than the standard of care, cinacalcet, and reduced serum PTH levels in mice without the hypocalcemia typical of CaSR drugs. As determined from cryo-electron microscopy structures, the PAMs identified here promote CaSR conformations that more closely resemble the activated state than those induced by the established drugs.

Activation of the Calcium-Sensing Receptor by a Subfraction of Amino Acids Contained in Thyroid Drainage Fluid.

Hypoparathyroidism is a common sequela of thyroid surgery; in this study, we aimed at exploring the pathogenesis behind it. The following premises suggest that wound fluid might be a causative agent. (i) Parathyroid hormone secretion is under feedback control by the calcium-sensing receptor, which responds to a diverse array of activating ligands. (ii) Postoperative hypoparathyroidism arises from a secretory deficiency of the parathyroid glands. Even in patients later unaffected by hypoparathyroidism, parathyroid hormone levels drop within hours after surgery. (iii) Wound fluid is bound to enter the tissue around the thyroid bed, where the parathyroid glands are located. Its composition is shaped by a series of proteolytic reactions triggered by wounding. Using thyroid drainage as a surrogate, we addressed the possibility that wound fluid contains compounds activating the calcium-sensing receptor. Drainage fluid ultrafiltrate was found to be rich in amino acids, and on separation by HPLC, compounds activating the calcium-sensing receptor partitioned with hydrophilic matter that rendered buffer acidic. The data show that glutamate and aspartate at millimolar concentrations supported activation of the calcium-sensing receptor, an effect contingent on low pH. In the presence of glutamate/aspartate, protons activated the calcium-sensing receptor with a pH50 of 6.1, and at pH 5, produced maximal activation. This synergistic mode of action was exclusive; glutamine/asparagine did not substitute for the acidic amino acids, nor did Ca2+ substitute for protons. NPS-2143, a negative allosteric receptor modulator completely blocked receptor activation by glutamate/aspartate and by fractionated drainage fluid. Thus, wound fluid may be involved in suppressing parathyroid hormone secretion.

Multiscale effects of the calcimimetic drug, etelcalcetide on bone health of rats with secondary hyperparathyroidism induced by chronic kidney disease

Chronic kidney disease-induced secondary hyperparathyroidism (CKD-SHPT) heightens fracture risk through impaired mineral homeostasis and elevated levels of uremic toxins (UTs), which in turn enhance bone remodeling. Etelcalcetide (Etel), a calcium-sensing receptor (CaSR) agonist, suppresses parathyroid hormone (PTH) in hyperparathyroidism to reduce excessive bone resorption, leading to increased bone mass. However, Etel's effect on bone quality, chemical composition, and strength is not well understood. To address these gaps, we established a CKD-SHPT rat model and administered Etel at a human-equivalent dose concurrently with disease induction. The effects on bone and mineral homeostasis were compared with a CKD-SHPT (vehicle-treated group) and a control group (rats without SHPT). Compared with vehicle-treated CKD-SHPT rats, Etel treatment improved renal function, reduced circulating UT levels, improved mineral homeostasis parameters, decreased PTH levels, and prevented mineralization defects. The upregulation of mineralization-promoting genes by Etel in CKD-SHPT rats might explain its ability to prevent mineralization defects. Etel preserved both trabecular and cortical bones with attendant suppression of osteoclast function, besides increasing mineralization. Etel maintained the number of viable osteocytes to the control level, which could also contribute to its beneficial effects on bone. CKD-SHPT rats displayed increased carbonate substitution of matrix and mineral, decreased crystallinity, mineral-to-matrix ratio, and collagen maturity, and these changes were mitigated by Etel. Further, Etel treatment prevented CKD-SHPT-induced deterioration in bone strength and mechanical behavior. Based on these findings, we conclude that in CKD-SHPT rats, Etel has multiscale beneficial effects on bone that involve remodeling suppression, mineralization gene upregulation, and preservation of osteocytes.

Hypercalcaemic Crisis Associated with Hyperthyroidism: A Rare and Challenging Presentation

A 51-year-old female with a history of multinodular goitre presented with vomiting, abdominal discomfort, and generalized tiredness. Investigations revealed hypercalcemia (ionized calcium 1.41 mmol/L), hypokalaemia, suppressed parathyroid hormone, and significantly elevated free thyroxine (> 7.77 ng/dL) with a suppressed thyroid-stimulating hormone level consistent with hyperthyroidism. Further, the workup confirmed Graves’ disease as the underlying aetiology. Hyperthyroidism is occasionally associated with mild to moderate hypercalcemia, but severe hypercalcemia or hypercalcaemic crisis is an extremely rare complication. Prompt recognition and treatment are crucial to prevent life-threatening complications. The patient was treated with intravenous fluids, a low-calcium diet, zoledronic acid, carbimazole, and a beta-blocker, leading to improvement in her condition. This case highlights a rare occurrence of hypercalcaemic crisis in a patient with thyrotoxicosis due to Graves’ disease. Hyperthyroidism-induced hypercalcemia requires prompt recognition and multidisciplinary management involving endocrinologists, internists, and critical care specialists to prevent potentially life-threatening complications. Healthcare providers should consider the hypercalcaemic crisis in the differential diagnosis of hypercalcemia in the context of hyperthyroidism.

Enzymatic hydrolysates from sea cucumber body wall prevent low calcium-induced osteoporosis by regulating calcium absorption and gut microbiota

Inadequate calcium intake or intestinal malabsorption is closely related to osteoporosis. The aim of this study was to investigate the effects of sea cucumber enzymatic hydrolysates (SCEH) prepared from body wall on calcium absorption in calcium-deficient rats. Fifty-six female Sprague-Dawley rats on a low calcium diet that induced osteoporosis were fed SCEH and calcium carbonate for 3 months. The results showed that oral administration of SCEH and calcium carbonate both increased the body weight (bw) and bone mineral density (BMD) in calcium-deficient rats to varying degrees, thereby alleviating the adverse effects of osteoporosis. In addition, oral administration of a combination of SCEH (2000 mg/kg bw/day) and calcium (333 mg/kg bw/day) upregulated the expression of calcium transporter genes (TRPV6 and Calbindin-D9k) in the intestines, increased serum 1,25(OH)2D3 levels and BMD, decreased trabecular bone separation, and inhibited parathyroid hormone (PTH) release in calcium-deficient rats compared to calcium carbonate groups. Thus, this combination promoted calcium absorption and improved the efficiency of calcium utilization. These results might be associated with a higher short chain fatty acid (SCFA) level in the gut and an increased abundance of butyrate and acetate producing bacteria, such as Christensenellaceae R7 group, UCG-005 and Clostridium UCG-014. Therefore, a diet containing SCEH and calcium combinations might be recommended to increase bone mass and inhibit osteoporosis.

Thiazide diuretics and primary hyperparathyroidism.

Thiazide diuretics exert a natriuretic and diuretic effect by inhibiting sodium reabsorption in the distal convoluted tubule. Furthermore, thiazide diuretics affect renal calcium handling by increasing calcium reabsorption, leading to hypocalciuria. The effect that thiazide diuretics exert on parathyroid hormone secretion is controversial. Some studies found parathyroid hormone levels were suppressed with the use of thiazide diuretics, while others found that thiazides were associated with initial parathyroid hormone suppression followed by raised parathyroid hormone levels. This makes the relationship between thiazide diuretics and primary hyperparathyroidism interesting. If a patient is taking thiazide diuretics, this may make it harder to establish the aetiology of hypercalcaemia and may unmask normocalcaemic or mild primary hyperparathyroidism. Thiazide diuretics may have a beneficial role in the diagnosis of patients with concomitant hyperparathyroidism and hypercalciuria by distinguishing secondary hyperparathyroidism caused by hypercalciuria from normocalcaemic primary hyperparathyroidism. In addition, thiazide diuretics may have a role in managing patients with primary hyperparathyroidism who have an indication for parathyroidectomy in view of significant hypercalciuria, but are unfit for surgery.

Kidney phosphate wasting predicts poor outcome in polycystic kidney disease.

Patients with autosomal dominant polycystic kidney disease (ADPKD) have disproportionately high levels of fibroblast growth factor 23 (FGF-23) for their chronic kidney disease stage, however only a subgroup develops kidney phosphate wasting. We assessed factors associated with phosphate wasting and hypothesize that it identifies patients with more severe disease and predicts disease progression. We included 604 patients with ADPKD from a multicenter prospective observational cohort (DIPAK; Developing Intervention Strategies to Halt Progression of Autosomal Dominant Polycystic Kidney Disease) in four university medical centers in the Netherlands. We measured parathyroid hormone (PTH) and total plasma FGF-23 levels, and calculated the ratio of tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) with <0.8 mmol/L defined as kidney phosphate wasting. We analysed the association of TmP/GFR with estimated GFR (eGFR) decline over time and the risk for a composite kidney outcome (≥30% eGFR decline, kidney failure or kidney replacement therapy). In our cohort (age 48±12 years, 39% male, eGFR 63±28 mL/min/1.73 m2), 59% of patients had phosphate wasting. Male sex [coefficient -0.2, 95% confidence interval (CI) -0.2; -0.1], eGFR (0.002, 95% CI 0.001; 0.004), FGF-23 (0.1, 95% CI 0.03; 0.2), PTH (-0.2, 95% CI -0.3; -0.06) and copeptin (-0.08, 95% CI -0.1; -0.08) were associated with TmP/GFR. Corrected for PTH, FGF-23 and eGFR, every 0.1 mmol/L decrease in TmP/GFR was associated with a greater eGFR decline of 0.2 mL/min/1.73 m2/year (95% CI 0.01; 0.3) and an increased hazard ratio of 1.09 (95% CI 1.01; 1.18) of the composite kidney outcome. Our study shows that in patients with ADPKD, phosphate wasting is prevalent and associated with more rapid disease progression. Phosphate wasting may be a consequence of early proximal tubular dysfunction and insufficient suppression of PTH.

Active Vitamin D Use and Fractures in Hemodialysis Patients: Results from the International DOPPS.

Active vitamin D is commonly used to control secondary hyperparathyroidism in dialysis patients, but it is unknown whether active vitamin D directly improves bone strength, independently of its ability to suppress parathyroid hormone (PTH). We analyzed the association between the prescription of active vitamin D and incidence of any fracture and hip fracture in 41,677 in-center hemodialysis patients from 21 countries in phases 3 to 6 (2005 to 2018) of the Dialysis Outcomes and Practice Patterns Study (DOPPS). We used Cox regression, adjusted for PTH and other potential confounders, and used a per-protocol approach to censor patients at treatment switch during follow-up. We also used a facility preference approach to minimize confounding by indication. Overall, 55% of patients were prescribed active vitamin D at study enrollment. Event rates (per patient-year) were 0.024 for any fracture and 0.010 for hip fracture. The adjusted hazard ratio (95% confidence interval) comparing patients prescribed versus not prescribed active vitamin D was 1.02 (0.90 to 1.17) for any fracture and 1.00 (0.81 to 1.23) for hip fracture. In the facility preference approach, there was no difference in fracture rate between facilities with higher versus lower active vitamin D prescriptions. Thus, our results do not suggest a PTH-independent benefit of active vitamin D in fracture prevention and support the current KDIGO guideline suggesting the use of active vitamin D only in subjects with elevated or rising PTH. Further research is needed to determine the role of active vitamin D beyond PTH control. © 2023 American Society for Bone and Mineral Research (ASBMR).

Secondary hyperparathyroidism in chronic kidney disease: pathomechanism and current treatment possibilities.

Secondary hyperparathyroidism (SHPT) is one of the most common metabolic complications resulting from chronic kidney disease (CKD). The complexity of calcium and phosphate disorders associated with CKD is defined by the Kidney Disease Improvement Global Outcomes (KDIGO) working group as CKD-related mineral and bone disorders (CKD-MBD). The last update of the KDIGO guidelines on the conduct in CKD-MBD was published in 2017. The treatment of SHPT is based on 2 strategies: counteracting hyperphosphataemia and suppressing parathyroid hormone (PTH) secretion. Therapy should be based on optimally selected drugs, taking into account additional effects to reduce the risk of chronic complications and side effects. The creation of new drugs with a better safety profile, significant reduction of side effects, and greater efficiency in achieving target serum phosphorus and PTH values forces the gradual replacement of existing treatment with new pharmacotherapies. The aim of this study is to discuss the latest issues (in connection with the latest KDIGO guidelines) regarding the pathomechanism of secondary hyperparathyroidism and the current directions of the therapy in these disorders.

Calcifediol in patients with hip fractures

Vitamin D deficiency has a high prevalence in the elderly population. This condition can cause sarcopenia and osteoporomalacia, which are associated with an increased risk of falls and fractures, especially of the proximal femur. These fractures have devastating consequences in terms of mortality, disability, and healthcare and social costs. Considering that 60% of hip fracture patients have hypovitaminosis D, and a serum 25(OH)D₃ increase of 10 ng/ml reduces the risk of hip fracture by 20%, correction of vitamin D status is clearly essential. Among the available preparations of vitamin D, calcifediol is preferred in cases with liver disease, malabsorption, obesity, and concomitant use of corticosteroids. Calcifediol administration corrects vitamin D deficiency and suppresses parathyroid hormone within 1 week, reaching the serum 25(OH)D₃ threshold of 30 ng/ml in 2 weeks. Correction of hypovitaminosis D with calcifediol also improves muscle strength and physical performance, reducing the risk of falls. Evidence about the role of calcifediol in the management of hip fracture patients is still scarce. Compared with placebo, administration of calcifediol in combination with strengthening exercise led to increased overall survival in patients with hip fracture. The efficacy of calcifediol in rapidly normalizing vitamin D status might be particularly useful in patients at imminent risk of fracture, such as those with hip fracture who need to receive immediate treatment with anti-osteoporotic drugs. KEY WORDS: Hip fractures, vitamin D deficiency, calcifediol, osteoporosis.

SAT244 Hypercalcemia Induced By Inconspicuous Histoplasmosis Infection

Abstract Disclosure: M. Alkhathlan: None. Y. Li: None. A. Siddiqui: None. S. Goud: None. Background: Hypercalcemia is a common condition with a variety of etiologies. In general, it can be categorized as either parathyroid hormone (PTH) dependent or independent. In those with non-PTH mediated hypercalcemia, elevated 1, 25 vitamin D is one of the causes and among pathologies behind it are sarcoidosis, malignancy, and to less extent infectious process. An important determinant in the management of elevated 1,25vitD is to identify the source of 1,25vitD overproduction as the choice of treatment can affect the outcomes and increase the risk of mortality. Clinical Case: Our patient is an 81-year-old man who had been admitted to the hospital for nonspecific fatigue and weakness for two months. He was discharged from another hospital with similar complaints without resolution. At the time of admission, he was noted to have elevated total calcium 12.5 mg/dL (8.4-10.2) with albumin 3.0 g/dL (3.5-5.2), subacute kidney injury with creatinine 3.46 mg/dL (0.7-1.3), suppressed parathyroid hormone (PTH) and markedly elevated 1,25-dihydroxy vitamin D (1,25OH2D) 128 pg/mL (19.9-79.3). His calcium and kidney function were normal 4 months ago. The hypercalcemia was refractory to intravenous fluid, loop diuretic or calcitonin administration. Extensive workup eventually revealed disseminated histoplasmosis infection with blood and urine positive for histoplasmosis antigens. Bone marrow aspiration showed scattered non-necrotizing granulomas. With antifungal treatment, his calcium level returned to the normal range in two weeks (8.9 mg/dL) and was maintained in the normal range. Conclusion: Hypercalcemia is a rare presentation of histoplasmosis. Pubmed keyword search of hypercalcemia and histoplasmosis returned 18 clinical case reports from 1977 to 2021. The case review showed a striking similarity in atypical clinical presentation and diagnosis challenges. Hypercalcemia is most developed in histoplasmosis disseminated cases with elevated 1,25vitD levels and pathology identification of granulomas in some of the cases. With successful antifungal treatment, patients will have prompt recovery of hypercalcemia. Steroid treatment is a well know and effective treatment by suppressing 1-alpha hydroxylation of 25-vitD. However, treatment with steroids before establishing diagnosis due to Inconspicuous presentations or delay in diagnosis may lead to mortality quickly. Presentation: Saturday, June 17, 2023

Bilateral giant parathyroid adenoma and hungry bone syndrome: a case report

BackgroundThere is some evidence supporting the idea that double parathyroid adenomas represent a different entity from multiglandular hyperplasia; however, the distinction among them is not straightforward.Case presentationWe described a case of primary hyperparathyroidism (PHPT) with pronounced clinical manifestations, caused by a bilateral giant parathyroid adenoma. A 34-year-old Hispanic/Latino male was diagnosed with PHPT caused by two giant parathyroid adenomas. The preoperative tests were neck ultrasound and computed tomography scan (CT-scan), showing two masses in the territory of parathyroid glands, bilaterally distributed (right was 31 × 18 × 19 mm and the left was 38 × 15 × 14 mm); sestamibi scan was not available. Parathyroid hormone (PTH) was highly elevated. Multiple complications of PHPT were present, such as bone lytic lesions, renal and pancreatic calcifications, and cardiovascular disease, the latter of which is an overlooked complication of PHPT. Multiple endocrine neoplasia 1 and 2 (MEN 1/2) were ruled out by the absence of clinical, biochemical, and radiological findings in other endocrine glands. The patient underwent subtotal parathyroidectomy with an intraoperative histopathological study; both intraoperative and definitive histopathology results were consistent with parathyroid adenomas; afterward, adequate suppression of PTH was assured, and later on, the patient presented hungry bone syndrome (HBS).ConclusionsThe diagnosis of double parathyroid adenomas is difficult. Regarding the similarities between multiglandular hyperplasia and parathyroid adenomas, this case report contributes to the further distinction between these two clinical entities. This case report also represents, in particular, the challenge of difficult diagnosis in places with limited resources, such as developing countries.

Pmma body injection and hypercalcemia correlation: a cross-sectional observational study on the comprehensive analysis of variables

Introduction: Hypercalcemia related to aesthetic intramuscular implants exclusively made of PMMA (polymethylmethacrylate) is a very rare condition. Late complications of these implants are related to poorly understood inflammatory triggers, which may reactivate stabilized implants, increase calcitriol production, and lead to hypercalcemia. Methods: Records of patients seen between 2022 and 2023 with a PMMA microsphere body implant and a subsequent diagnosis of hypercalcemia were searched. Medical history, medication use, data on PMMA implantation, and laboratory tests related to calcium metabolism were described and subjected to variable correlation analysis. The instituted treatments were described. Results: A total of 17 female patients with exclusive body PMMA implants confirmed by ultrasonography or MRI (Magnetic Resonance Image) developed hypercalcemia between 2017 and 2022. Prior renal disease, COVID-19 infection, vitamin D use, and anabolic steroid use correlated with laboratory changes in hypercalcemia. Larger PMMA implant volumes led to parathyroid hormone suppression. Conclusion: Patients with PMMA body implants may rarely present with hypercalcemia when variables such as renal disease before implantation, high doses of vitamin D or anabolic steroids are present. Based on the data presented and the available scientific literature, recommendations for patient investigation, implant volume limit, and patient follow-up after the procedure were made.

Why is childhood urolithiasis increasing? Etiology, diagnosis and management: a single-center experience.

Globally, urolithiasis is becoming more and more common among children. We aimed to determine the etiology, and the diagnostic and therapeutic approaches in patients with urolithiasis. This was a retrospective study which included all patients (aged 1month-18years) admitted to the pediatric nephrology clinic in Elazığ Fethi Sekin City Hospital with urolithiasis between November 2019 and 2021. Only patients whose diagnosis of urolithiasis was confirmed by urinary ultrasonography were included in the study, while patients with chronic diseases (neurological diseases such as epilepsy, cerebral palsy, chronic bowel diseases, etc.) predisposing to kidney stone formation were not. Demographic characteristics, serum and urine biochemical parameters, urine metabolic and kidney stone metabolic and chemical analyses, urinary tract ultrasonography findings and treatment modalities were collected. One hundred ninety-seven patients (91 female and 106 male) were included in the study. Hypervitaminosis D was detected in 4 (2%) patients, suppressed parathyroid hormone in 12 (6%) and hypercalcemia in 27 (14%) patients. Metabolic screening showed hypercalciuria in 69 (35%) patients, hypocitraturia in 39 (20%), hyperoxaluria in 15 (8%) and cystinuria in 6 (3%) patients. Eighty three (42%) patients had a positive family history for kidney stones. One hundred eighteen (60%) patients received potassium citrate treatment, 71 (36%) were given hydration and diet recommendations without medical treatment, 6 (3%) received tiopronin treatment, and 2 (1%) patients were treated surgically. Our study suggests that Vitamin D supplementation at doses higher than 400IU/day may be a risk factor for kidney stonesin children. We observed that mothers tend not to give water to infants who are breastfed or formula-fed in the first year of life. K-citrate treatment can be a good option for prevention and dissolution of stones by alkalinization.

Abstract #1406508: A Rare Case of Calcitriol-mediated Hypercalcemia in a Patient with Pneumocystis Jiroveci Pneumonia and the Role of Steroids in its Management

Calcitriol-mediated hypercalcemia is an uncommon complication of Pneumocystis jiroveci pneumonia (PJP). Some cases of PJP have been reported in patients with solid organ transplants and AIDS. Here we present a case of calcitriol-mediated hypercalcemia due to granulomatous Pneumocystis jiroveci pneumonia in a patient with a history of multiple sclerosis. A 45-year-old man with a medical history of multiple sclerosis, spondyloarthritis, smoking, and bipolar disorder was admitted for the evaluation of fever, fatigue, constipation, confusion, and weight loss of 10 Lbs over three months. His medications include rituximab, methotrexate, vitamin D-4000 IU, lithium, and calcium carbonate-600 mg. Laboratory evaluation showed elevated serum calcium (15 mg/dl) with a suppressed parathyroid hormone (9 pg/mL). Other pertinent findings include mildly elevated 25-hydroxyvitamin D (87 ng/ml), significantly elevated 1,25-dihydroxyvitamin D (381 pg/ml), and normal PTHrP (<2 pmol/L), vitamin A (0.82 mg/L) and TSH (1.31 mU/L). Extensive workup including AFB smear for tuberculosis, ACE level for sarcoidosis, SPEP for multiple myeloma, leukemia-lymphoma flow cytometry, and CT chest and PET-CT for malignancy were unremarkable. Treatment with large-volume intravenous fluids, calcitonin, and zoledronic acid followed by denosumab showed a transient reduction in serum calcium level to 10.5 mg/dl in 2 days and a rebound to a peak of 15.4 mg/dl in a week. Bronchoscopy with bronchoalveolar lavage which was done for persistent fever and new onset hypoxia revealed PJP confirmed by PCR. With this new finding, the diagnosis of PJP-induced calcitriol-mediated hypercalcemia was considered. He was then treated with Bactrim and prednisone 60 mg daily. Due to the severity of hypercalcemia, he required a hemodialysis session while waiting for the medications to take effect. His calcium normalized a week after the initiation of steroids and antibiotics and he was discharged on a slow prednisone taper. Clinic follow-up 4 weeks after discharge showed normal calcium, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D levels. Discontinuation of prednisone was attempted but resulted in rebound elevation of 1,25-dihydroxyvitamin D requiring continuation of low-dose prednisone 5 mg. Our immunocompromised patient developed hypercalcemia induced by PJP infection due to granulomatous production of 1α-hydroxylase resulting in increased calcitriol formation. Steroids unsurprisingly appear to have the best impact on PJP-induced hypercalcemia because of their anti-inflammatory property. In this clinical entity, it inhibits inflammation and granuloma formation leading to a reduction in the release of 1α-hydroxylase and 1,25-dihydroxyvitamin D levels. It is essential to consider PJP as an etiology of hypercalcemia, especially in immunosuppressed patients. Steroid appears to be effective medical therapy in this setting. The timing and duration of treatment, and the efficacy of bisphosphonates and denosumab, require further studies.

An interesting case of unintentional vitamin D toxicity in an infant due to erroneous supplement concentration: a case report.

Here, we present a case of a 2.5-month-old infant presenting with failure to thrive. The clinical presentations were nasal blockage, noisy breathing, poor feeding, lethargy, dehydration, and fever for 3 days with decreased appetite. Her urine culture report showed a urinary tract infection. The biochemical evaluation demonstrated raised total serum calcium (6.0mmol/l) and serum 25-hydroxy vitamin D (>160ng/ml) with suppressed parathyroid hormone concentration (3.7pg/ml), which was the major concern to the clinicians. On ultrasonographical examination, nephrocalcinosis was observed. Further evaluation unveiled that the vitamin D supplement administered to the infant constituted a deucedly high dose of 42000IU instead of the recommended dose of 0.5ml of 800IU. The patient developed vitamin D toxicity after consuming a mega dose of vitamin D supplements due to a manufacturer error. Hypervitaminosis D has severe life-threatening consequences like failure to thrive in otherwise healthy-born infants. Regular monitoring of vitamin D supplements administered in infants by medicinal practitioners and strict supervision of all stages of the production process by pharmaceutical companies is crucial to prevent complications from supplement overdose.

Nephrolithiasis and Multicystic Kidneys in a Young Patient: A Quiz

Nephrolithiasis and Multicystic Kidneys in a Young Patient: A Quiz

An uncanny case of paraneoplastic calcitriol mediated hypercalcaemia.

A 77-year-old female patient with a history of treated breast cancer and a recently diagnosed laryngeal cancer presented with severe hypercalcaemia associated with suppressed parathyroid hormone (PTH) levels. Her initial investigations included 25-hydroxy vitamin D levels, short synacthen test, bone scan, myeloma screen and thyroid function tests which were within normality. A computerised tomography (CT) scan showed some right lung apical fibrotic changes. Her PTH-related peptide (PTHrP) was normal and sarcoidosis was also excluded. Her previous and current malignancies were thought to be unlikely behind her hypercalcaemia. Her 1,25-dihydroxy vitamin D (calcitriol) levels were found to be elevated. Her hypercalcaemia was initially managed with intravenous fluids and intermittent bisphosphonates infusions which would transiently reduce her calcium levels. Steroid treatment was initiated which improved her hypercalcaemia; however, the calcium levels rebounded on tapering the steroids down, a pre-requisite prior to a positron emission computerised tomography (PET-CT) scan to determine the source of the excess calcitriol production. This was cancelled following an emergency admission with marked hypercalcaemia and acute renal and liver injury. A contemporary CT scan showed a right apical lung mass with hepatic lesions suggestive of a disseminated lung primary. The histology obtained from a liver biopsy was compatible with metastatic small-cell lung carcinoma. Unfortunately, her clinical condition deteriorated further and she did not survive. To the best of our knowledge, this is the first report in the literature describing calcitriol-mediated hypercalcaemia due to a small-cell lung cancer. Paraneoplastic hypercalcaemia may manifest even without overt detection of the primary cancer. The workup for paraneoplastic hypercalcaemia should be meticulous. Both bisphosphonates and steroids are useful in the initial management of calcitriol-mediated hypercalcaemia, but the definitive management is the treatment of the cause.